Composite stent having multi-axial flexibility and method of manufacture thereof

ABSTRACT

A bioabsorbable composite stent structure, comprising bioabsorbable polymeric ring structures which retain a molecular weight and mechanical strength of a starting substrate and one or more interconnecting struts which extend between and couple adjacent ring structures. The ring structures can have a formed first diameter and being radially compressible to a smaller second diameter and re-expandable to the first diameter. The ring structures can comprise a base polymeric layer. The interconnecting struts can be formed from a polymer blend or co-polymer of poly-L-lactide (PLLA) and an elastomeric polymer. The interconnecting struts each can have a width that is less than a circumference of one of the ring structures. The adjacent ring structures can be axially and rotationally movable relative to one another via the interconnecting struts. The interconnecting struts can also be bioabsorbable.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 15/439,002, filed on Feb. 22, 2017, which is a continuation ofU.S. patent application Ser. No. 13/476,853, filed on May 21, 2012,which is a divisional of U.S. patent application Ser. No. 12/143,659,filed on Jun. 20, 2008 (now U.S. Pat. No. 8,206,635 issued Jun. 26,2012) and a continuation-in-part of U.S. patent application Ser. No.12/541,095, filed on Aug. 13, 2009, which claims the benefit of priorityto U.S. Prov. Pat. App. No. 61/088,433, filed on Aug. 13, 2008, all ofwhich are incorporated herein by reference in their entireties.

TECHNICAL FIELD

The present invention relates generally to composite prostheses whichare implantable within a patient. More particularly, the presentinvention relates to implantable prostheses which utilize a compositestructure having various geometries suitable for implantation within anartery of a patient, such as the superficial femoral artery (SFA) of thepatient.

BACKGROUND

In recent years there has been growing interest in the use of artificialmaterials, in particular, materials formed from polymers, for use inimplantable devices that come into contact with bodily tissues or fluidsparticularly blood. Some examples of such devices are artificial heartvalves, stents, and vascular prosthesis. Some medical devices such asimplantable stents which are fabricated from a metal have beenproblematic in fracturing or failing after implantation. Moreover,certain other implantable devices made from polymers have exhibitedproblems such as increased wall thickness to prevent or inhibit fractureor failure. However, stents having reduced wall thickness are desirableparticularly for treating arterial diseases.

Because many polymeric implants such as stents are fabricated throughprocesses such as extrusion or injection molding, such methods typicallybegin the process by starting with an inherently weak material. In theexample of a polymeric stent, the resulting stent can have imprecisegeometric tolerances as well as reduced wall thicknesses which can makethese stents susceptible to brittle fracture.

A stent which is susceptible to brittle fracture is generallyundesirable because of its limited ability to collapse for intravasculardelivery as well as its limited ability to expand for placement orpositioning within a vessel. Moreover, such polymeric stents alsoexhibit a reduced level of strength. Brittle fracture is particularlyproblematic in stents as placement of a stent onto a delivery balloon orwithin a delivery sheath imparts a substantial amount of compressiveforce in the material comprising the stent. A stent made of a brittlematerial can crack or have a very limited ability to collapse or expandwithout failure. Thus, a certain degree of malleability is desirable fora stent to expand, deform, and maintain its position securely within thevessel.

Certain indications, such as peripheral arterial disease, affectsmillions of people where the superficial femoral artery (SFA) iscommonly involved. Stenosis or occlusion of the SFA is a common cause ofmany symptoms such as claudication and is often part of critical limbischemia. Although interventional therapy for SFA diseases using Nitinolstents is increasing, the SFA poses particular problems with respect tostent implantation because the SFA typically elongates and foreshortenswith movement, can be externally compressed, and is subject to flexion.Limitations of existing stents include, e.g., insufficient radialstrength to withstand elastic recoil and external compression, kinking,and fracture.

Because of such limitations, stent fractures have been reported to occurin the iliac, popliteal, subclavian, pulmonary, renal, and coronaryarteries. However, it is suspected that these fractures can occur at ahigher rate in the SFA than the other locations. For example, becausethe SFA can undergo dramatic non-pulsatile deformations (e.g., axialcompression and extension, radial compression, bending, torsion, etc.)such as during hip and knee flexion causing significant SFA shorteningand elongation and because the SFA has a tendency to develop long,diffuse, disease states with calcification requiring the use of multipleoverlapping stents, stent placement, maintenance, and patency isdifficult. Moreover, overlapping of adjacent stents cause metal-to-metalstress points that can initiate a stent fracture.

Accordingly, there is a need for an implantable stent that is capable ofwithstanding the dynamic loading conditions of the SFA and other similarenvironments.

SUMMARY

When a stent is placed into a vessel, particularly vessels such as thesuperficial femoral artery (SFA), iliac, popliteal, subclavian,pulmonary, renal, or the coronary arteries, the stent's ability to bendand compress is reduced. Moreover, such vessels typically undergo agreat range of motion requiring stents implanted within these vessels tohave an axial flexibility which allows for its compliance with thearterial movement without impeding or altering the physiological axialcompression and bending normally found with positional changes.

A composite stent structure having one or more layers of bioabsorbablepolymers can be fabricated with the desired characteristics forimplantation within these vessels. Each layer can have a characteristicthat individually provides a certain aspect of mechanical behavior tothe stent such that the aggregate layers form a composite polymericstent structure capable of withstanding complex, multi-axial loadingconditions imparted by an anatomical environment such as the SFA.

Generally, a tubular substrate can be constructed by positioning one ormore high-strength bioabsorbable polymeric ring structures spaced apartfrom one another along a longitudinal axis. The ring structures can beconnected to one another by one or more layers of polymeric substrates,such as bioabsorbable polymers which are also elastomeric. Such astructure is made of several layers of bioabsorbable polymers with eachlayer having a specific property that positively affects certain aspectsof the mechanical behavior of the stent and all layers collectively as acomposite polymeric material creates a structure capable of withstandingthe complex, multi-axial loading conditions of an anatomical environmentsuch as the SFA.

A number of casting processes can be utilized to develop substrates,such as cylindrically shaped substrates having a relatively high levelof geometric precision and mechanical strength for forming theaforementioned ring structures. These polymeric substrates can then bemachined using any number of processes (e.g., high-speed laser sources,mechanical machining, etc.) to create devices such as stents having avariety of geometries for implantation within a patient, such as theperipheral or coronary vasculature of the patient.

An example of such a casting process is to utilize a dip-coatingprocess. The utilization of dip-coating results in polymeric substrateswhich are able to retain the inherent properties of the startingmaterials. This in turn results in polymeric substrates having arelatively high radial strength which is retained through any additionalmanufacturing processes for implantation. Additionally, dip-coating alsoallows for the creation of polymeric substrates having multiple layers.

In using dip-coating to form the polymeric substrate, one or more highmolecular weight biocompatible and/or bioabsorbable polymers can beselected for forming upon a mandrel. The one or more polymers can bedissolved in a compatible solvent in one or more correspondingcontainers such that the appropriate solution can be placed under themandrel. The substrate can be formed to have multiple layers overlaidupon one another such that the substrate has a first layer of a firstpolymer, a second layer of a second polymer, and so on depending uponthe desired structure and properties of the substrate. Thus, the varioussolutions and containers can be replaced beneath the mandrel betweendip-coating operations in accordance with the desired layers to beformed upon the substrate such that the mandrel can be dippedsequentially into the appropriate polymeric solution.

Parameters such as the number of times the mandrel is immersed, thesequence and direction of dipping, the duration of each immersion, thedelay time between each immersion, or the drying or curing time betweendips can each be controlled to yield a substrate having the desiredmechanical characteristics. For example, the dip-coating process can beused to form a polymeric substrate having half the wall thickness of asubstrate formed from extrusion while retaining an increased level ofstrength in the polymeric substrate.

The immersion times as well as the drying times can be uniform betweeneach immersion or can be varied as determined by the desired propertiesof the resulting substrate. Moreover, the substrate can be placed in anoven or dried at ambient temperatures between each immersion or afterthe final immersion to attain a predetermined level of crystals (e.g.,60%) and a predetermined level of amorphous polymeric regions (e.g.,40%). Each of the layers overlaid upon one another during thedip-coating process can be tightly adhered to one another and the wallthicknesses and mechanical properties of each polymer can be retained intheir respective layer with no limitation on the molecular weight and/orcrystalline structure of the polymers utilized.

Dip-coating can also be used to impart an orientation between layers(e.g., linear orientation by dipping, radial orientation by spinning themandrel, etc.) to further enhance the mechanical properties of theformed substrate. As radial strength is a desirable attribute of stentdesign, post-processing of the formed substrate can be accomplished toimpart such attributes. Typically, polymeric stents suffer from havingrelatively thick walls to compensate for the lack of radial strength,and this, in turn, reduces flexibility, impedes navigation, and reducesarterial luminal area immediately post implantation. Post-processing canalso help to prevent material creep and recoil which are problemstypically associated with polymeric stents. Creep is a time-dependentpermanent deformation that occurs to a specimen under stress, typicallyunder elevated temperatures.

For post-processing, a predetermined amount of force can be applied tothe substrate where such a force can be generated by a number ofdifferent methods. One method is by utilizing an expandable pressurevessel placed within the substrate. Another method is by utilizing abraid structure, such as a braid made from a super-elastic or shapememory alloy, such as Nitinol, to increase in size and to apply thedesirable degree of force against the interior surface of the substrate.

Yet another method can apply the expansion force by application of apressurized inert gas such as nitrogen within the substrate lumen. Acompleted substrate can be placed inside a molding tube which has aninner diameter that is larger than the cast cylinder. A distal end ordistal portion of the cast cylinder can be clamped or otherwise closedand a pressure source can be coupled to a proximal end of the castcylinder. The entire assembly can be positioned over a nozzle whichapplies heat to either the length of the cast cylinder or to a portionof cast cylinder. The increase in diameter of the cast cylinder can thusrealign the molecular orientation of the cast cylinder to increase itsradial strength. After the diameter has been increased, the castcylinder can be cooled.

The molecular weight of a polymer is typically one of the factors indetermining the mechanical behavior of the polymer. With an increase inthe molecular weight of a polymer, there is generally a transition frombrittle to ductile failure. A mandrel can be utilized to cast ordip-coat the polymeric substrate. Further examples of high-strengthbioabsorbable polymeric substrates formed via dip-coating processes aredescribed in further detail in U.S. patent application Ser. No.12/143,659 filed Jun. 20, 2008, which is incorporated herein byreference in its entirety.

The substrate can also be machined, e.g., using laser ablationprocesses, to produce stents with suitable geometries for particularapplications. The composite stent structure can have a relatively highradial strength as provided by the polymeric ring structures while thepolymeric portions extending between the adjacent ring structures canallow for elastic compression and extension of the stent structureaxially as well as torsionally when axial and rotational stresses areimparted by ambulation and positional changes from the vessel upon thestent structure.

Also disclosed is a bioabsorbable composite stent structure comprisingbioabsorbable polymeric ring structures and one or more interconnectingstruts which extend between and couple adjacent ring structures. Thepolymeric ring structures can retain a molecular weight and mechanicalstrength of a starting substrate. The ring structures can be formed at afirst diameter and be radially compressible to a smaller seconddiameter. The ring structures can also be re-expandable to the firstdiameter. The ring structures can be separated from one another andcomprise a base polymeric layer. The base polymeric layer can be abioabsorbable polymeric substrate formed via a dip-coating process.

The one or more interconnecting struts can extend between and coupleadjacent ring structures. Each of the interconnecting struts can have awidth which is less than a circumference of one of the ring structures.The interconnecting struts can be formed from or comprise a polymerblend or co-polymer of poly-L-lactide (PLLA) and an elastomeric polymer.

The adjacent ring structures can be axially and rotationally movablerelative to one another via the interconnecting struts. The one or moreinterconnecting struts can also be bioabsorbable such that the entirecomposite stent structure can be bioabsorbable.

In one variation, the elastomeric polymer can be or comprisepolycaprolactone (PCL). The PCL can be about 1% to about 10% of thepolymer blend or co-polymer. In other variations, the PCL can be about1% to about 50% of the polymer blend or co-polymer. In certainvariations, the polymer blend or co-polymer can have a glass transitiontemperature between 50° C. and 65° C.

The ring structures can be spaced closer to one another along a firstportion than along a second portion of the stent structure. A terminalring structure can be relatively more flexible than a remainder of thering structures.

Another bioabsorbable composite stent structure is disclosed comprisingbioabsorbable polymeric ring structures and a plurality ofinterconnecting struts which extend between and couple adjacent ringstructures. The polymeric ring structures can retain a molecular weightand mechanical strength of a starting substrate. The ring structures canbe formed at a first diameter and be radially compressible to a smallersecond diameter. The ring structures can also be re-expandable to thefirst diameter. The ring structures can be separated from one anotherand comprise a base polymeric layer. The base polymeric layer can be abioabsorbable polymeric substrate formed via a dip-coating process.

The plurality of interconnecting struts can extend between and coupleadjacent ring structures. Each of the interconnecting struts can have awidth which is less than a circumference of one of the ring structures.The plurality of interconnecting struts can be formed from or comprise apolymer blend or co-polymer of poly-L-lactide (PLLA) and an elastomericpolymer. The plurality of interconnecting struts can be positioned alonga length of the composite stent structure in a circumferentiallyalternating manner between immediately adjacent ring structures.

The adjacent ring structures can be axially and rotationally movablerelative to one another via the interconnecting struts. The one or moreinterconnecting struts can also be bioabsorbable such that the entirecomposite stent structure can be bioabsorbable.

The elastomeric polymer making up part of the polymer blend orco-polymer can be or comprise polycaprolactone (PCL). The PCL can beabout 1% to about 10% of the polymer blend or co-polymer. In othervariations, the PCL can be about 1% to about 50% of the polymer blend orco-polymer. In certain variations, the polymer blend or co-polymer canhave a glass transition temperature between 50° C. and 65° C.

The ring structures can be spaced closer to one another along a firstportion than along a second portion of the stent structure. A terminalring structure can be relatively more flexible than a remainder of thering structures.

Yet another bioabsorbable composite stent structure is disclosedcomprising bioabsorbable polymeric ring structures and one or moreinterconnecting struts which extend between and couple adjacent ringstructures. The polymeric ring structures can retain a molecular weightand mechanical strength of a starting substrate. The ring structures canbe formed at a first diameter and be radially compressible to a smallersecond diameter. The ring structures can also be re-expandable to thefirst diameter. The ring structures can be separated from one anotherand comprise a base polymeric layer. The base polymeric layer can be abioabsorbable polymeric substrate formed via a dip-coating process.

The one or more interconnecting struts can extend between and coupleadjacent ring structures. Each of the interconnecting struts can have awidth which is less than a circumference of one of the ring structures.The interconnecting struts can be formed from or comprise a polymerblend or co-polymer of poly-L-lactide (PLLA) and an elastomeric polymer.The one or more interconnecting struts can be more elastic than the ringstructures.

The adjacent ring structures can be axially and rotationally movablerelative to one another via the interconnecting struts. The one or moreinterconnecting struts can also be bioabsorbable such that the entirecomposite stent structure can be bioabsorbable.

The elastomeric polymer making up part of the polymer blend orco-polymer can be or comprise polycaprolactone (PCL). The PCL can beabout 1% to about 10% of the polymer blend. In other variations, the PCLcan be about 1% to about 50% of the polymer blend or co-polymer. Incertain variations, the polymer blend or co-polymer can have a glasstransition temperature between 50° C. and 65° C.

The ring structures can be spaced closer to one another along a firstportion than along a second portion of the stent structure. A terminalring structure can be relatively more flexible than a remainder of thering structures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates an example of a polymeric substrate having one ormore layers formed by dip coating processes creating a substrate havinga relatively high radial strength and ductility.

FIG. 1B illustrates an example the formed polymeric substrate cut ormachined into a number of circular ring-like structures.

FIG. 2A illustrates an example of a dip-coating assembly or device whichcan be utilized to form any variation of the polymeric substratesdisclosed herein.

FIG. 2B illustrates another example of a dip-coating assembly or devicewhich can be utilized to form any variation of the polymeric substratesdisclosed herein.

FIG. 2C illustrates yet another example of a dip-coating assembly ordevice which can be utilized to form any variation of the polymericsubstrates disclosed herein.

FIGS. 3A to 3B illustrate partial cross-sectional side views of aportion of an example multi-layer polymeric substrate disclosed herein.

FIG. 3C illustrates a cross-sectional end view of a portion of anexample multi-layer polymeric substrate disclosed herein.

FIG. 4A illustrates an example of a polymeric base substrate which canbe utilized to form any variation of the polymeric stents or scaffoldsdisclosed herein.

FIG. 4B illustrates an example of how the circular ring-like structurescan be positioned or fitted upon a polymeric base substrate to form anintermediate layer of a composite stent structure.

FIG. 4C illustrates an example composite structure formed with anadditional polymeric layer overlaid atop the polymeric base substrateand ring structures.

FIG. 5 illustrates an example composite structure where the ringstructures can be patterned to form a scaffold structure.

FIG. 6 illustrates an example composite structure where ring structurescan be alternated between rings fabricated from different polymericsubstrates.

FIG. 7 illustrates an example composite structure where one or moreflexible terminal rings can be formed for overlapping between adjacentlydeployed stents.

FIG. 8 illustrates an example composite structure where each ringstructure along the composite stent can be fabricated from polymericsubstrates different from one another.

FIG. 9 illustrates an example composite structure where the intermediatepolymeric layer is formed as longitudinal strips rather than ringstructures.

FIG. 10 illustrates an example composite structure where theintermediate polymeric layer is formed as a helical structure betweenthe base layer and overlaid layer.

FIG. 11A illustrates an example of adjacent composite structuresdeployed within a vessel with a gap or spacing between the twostructures.

FIG. 11B illustrates another example of adjacent composite structuresdeployed within a vessel with the terminal ends of the structuresoverlapping with one another.

FIG. 12 illustrates a side view of an example composite structure wherethe terminal ring structures are configured to degrade at a relativelyfaster rate than the remaining ring structures.

FIGS. 13A and 13B illustrate side views of an example compositestructure where polymeric ring structures are positioned along aflexible base coat in a separate manufacturing operation.

FIGS. 14A and 14B illustrate partial cross-sectional side and end views,respectively, of a composite structure formed by sandwiching ahigh-strength polymeric material between two or more layers of aflexible polymer to provide for greater flexibility under radial stresswhile retaining relatively high strength.

FIG. 15A illustrates a perspective view of an example polymericsubstrate.

FIG. 15B illustrates the polymeric substrate of FIG. 15A machined intosegments having reduced diameters.

FIG. 15C illustrates a perspective view of an example of the machinedsubstrate further coated by one or more polymeric layers.

FIG. 15D illustrates a perspective partial cutaway view of an example ofthe machined substrate further coated by one or more polymeric layers.

FIG. 16 illustrates a portion of an example of a stent or scaffold whichcan be formed from any of the polymeric substrates disclosed hereinhaving ring structures connected by struts.

FIG. 17 illustrates a portion of another example of a stent or scaffoldwhich can be formed from any of the polymeric substrates disclosedherein having ring structures connected by struts.

FIGS. 18A and 18B illustrate an example polymeric substrate which hasbeen machined to form ring segments connected via connecting members.

FIGS. 18C and 18D illustrate an example of the machined substrate coatedby one or more polymeric layers and a partial cutaway view of themachined substrate coated by the one or more polymeric layers,respectively.

FIG. 19 illustrates a portion of another example of a stent or scaffoldwhich can be formed from any of the polymeric substrates disclosedherein having ring structures connected by struts.

FIG. 20 illustrates a portion of another example of a stent or scaffoldwhich can be formed from any of the polymeric substrates disclosedherein having ring structures connected by struts.

DETAILED DESCRIPTION

When a stent is placed into a vessel such as the superficial femoralartery (SFA), iliac, popliteal, subclavian, pulmonary, renal, orcoronary arteries, the stent's ability to bend and compress is reduced.Moreover, such vessels typically undergo a great range of motionrequiring stents implanted within these vessels to have an axialflexibility which allows for the stent to comply with certain vesselmovements without impeding or altering the physiological compression andbending of such vessels.

A composite stent structure having one or more layers of bioabsorbablepolymers can be fabricated with the desired characteristics forimplantation within these vessels. Each layer can have a characteristicthat individually provides a certain aspect of mechanical behavior tothe stent such that the aggregate layers form a composite polymericstent structure capable of withstanding complex, multi-axial loadingconditions imparted by an anatomical environment such as the SFA.

Generally, a tubular substrate can be constructed by positioning one ormore high-strength bioabsorbable polymeric ring structures spaced apartfrom one another along a longitudinal axis. The ring structures can beconnected to one another by one or more layers of polymeric substrates,such as bioabsorbable polymers which are also elastomeric. The substratecan also be machined, e.g., using laser ablation processes, to producestents with suitable geometries for particular applications. Thecomposite stent structure can have a relatively high radial strength asprovided by the polymeric ring structures while the polymeric portionsextending between the adjacent ring structures can allow for elasticcompression and extension of the stent structure axially as well astorsionally when axial and rotational stresses are imparted byambulation and positional changes from the vessel upon the stentstructure.

In manufacturing the polymeric ring structures from polymeric materialssuch as biocompatible and/or biodegradable polymers (e.g., poly-L-lacticacid (PLLA) 2.4, PLLA 4.3, PLLA 8.4, PLA, PLGA, etc.), a number ofcasting processes can be utilized to develop substrates, e.g.,cylindrically shaped substrates, having a relatively high level ofgeometric precision and mechanical strength. A high-strength tubularmaterial which exhibits a relatively high degree of ductility can befabricated utilizing such polymers having a relatively high molecularweight These polymeric substrates can then be machined using any numberof processes (e.g., high-speed laser sources, mechanical machining,etc.).

An example of such a casting process is to utilize a dip-coatingprocess. The utilization of dip-coating to create a base polymericsubstrate 10, as illustrated in FIG. 1A, having such desirablecharacteristics results in substrates 10 which are able to retain theinherent properties of the starting materials. This, in turn, results insubstrates 10 having a relatively high radial strength which is mostlyretained through any additional manufacturing processes forimplantation. Additionally, dip-coating the polymeric substrate 10 alsoallows for the creation of substrates having multiple layers. Themultiple layers can be formed from the same or similar materials or theycan be varied to include any member of additional agents, such as one ormore drugs for treatment of the vessel, as described in further detailbelow. Moreover, the variability of utilizing multiple layers for thesubstrate can allow one to control other parameters, conditions, orranges between individual layers such as varying the degradation ratebetween layers while maintaining the intrinsic molecular weight andmechanical strength of the polymer at a high level with minimaldegradation of the starting materials.

Because of the retention of molecular weight and mechanical strength ofthe starting materials via the casting or dip-coating process, polymericsubstrates 10 can be formed which enable the fabrication of devices suchas stents with reduced wall thickness which is highly desirable for thetreatment of arterial diseases. Furthermore, these processes can producestructures having precise geometric tolerances with respect to wallthicknesses, concentricity, diameter, etc.

One mechanical property in particular which is generally problematic forpolymeric stents formed from polymeric substrates is failure via brittlefracture of the device when placed under stress within the patient body.It is generally desirable for polymeric stents to exhibit ductilefailure under an applied load rather via brittle failure, especiallyduring delivery and deployment of a polymeric stent from an inflationballoon or constraining sheath. Further examples of high-strengthbioabsorbable polymeric substrates formed via dip-coating processes aredescribed in further detail in U.S. patent application Ser. No.12/143,659 filed Jun. 20, 2008, which is incorporated herein byreference in its entirety.

Such dip-coating methods can be utilized to create polymeric substratessuch as base polymeric substrate 10, which can then be cut into aplurality of polymeric ring structures 12, as shown in FIG. 1B. Thesering structures can have a width which varies depending upon theapplication and vessel and can range generally from 1 mm to 10 mm inwidth. Moreover, because the initial polymeric substrate or basepolymeric substrate 10 is formed upon a mandrel, substrate 10 and theresulting ring structures 12 can be formed to have an initial diameterranging generally from 2 mm to 10 mm.

An example of a dip-coating assembly 30 which can be utilized to cast ordip-coat the polymeric substrate is illustrated in the side view of FIG.2A. The dip-coating assembly 30 can comprise a base 32 supporting acolumn 34 which houses a drive column 36 and a bracket arm 38. Motor 42can urge drive column 36 vertically along column 34 to move bracket arm38 accordingly. Mandrel 40 can be attached to bracket arm 38 abovecontainer 44 which can be filled with a polymeric solution 46 (e.g.,PLLA, PLA, PLGA, etc.) into which mandrel 40 can be dipped via a linearmotion 52. The one or more polymers can be dissolved in a compatiblesolvent in one or more corresponding containers 44 such that theappropriate solution can be placed under mandrel 40. An optional motor48 can be mounted along bracket arm 38 or elsewhere along assembly 30 toimpart an optional rotational motion 54 to mandrel 40 and the substrate10 formed along mandrel 40 to impart an increase in the circumferentialstrength of substrate 10 during the dip-coating process, as described infurther detail below.

The assembly 30 can be isolated on a vibration-damping or vibrationallyisolated table to ensure that the liquid surface held within container44 remains completely undisturbed to facilitate the formation of auniform thickness of polymer material along mandrel 40 and/or substrate10 with each deposition The entire assembly 30 or just a portion of theassembly such as the mandrel 40 and polymer solution can be placed in aninert environment such as a nitrogen gas environment while maintaining avery low relative humidity (RH) level, e.g., less than 30% RH, andappropriate dipping temperature, e.g., at least 20° C. below the boilingpoint of the solvent within container 44 so as to ensure adequatebonding between layers of the dip-coated substrate. Multiple mandrelscan also be mounted along bracket arm 38 or directly to column 34.

The mandrel 40 can be sized appropriately and define a cross-sectionalgeometry to impart a desired shape and size to the substrate 10. Mandrel40 can be generally circular in cross section although geometries can beutilized as desired. In one example, mandrel 40 can define a circulargeometry having a diameter ranging from 1 mm to 20 mm to form apolymeric substrate having a corresponding inner diameter. Moreover,mandrel 40 can be made generally from various materials which aresuitable to withstand dip-coating processes, e.g., stainless steel,copper, aluminum, silver, brass, nickel, titanium, etc. The length ofmandrel 40 that is dipped into the polymer solution can be optionallylimited in length by, e.g., 50 cm, to ensure that an even coat ofpolymer is formed along the dipped length of mandrel 40 to limit theeffects of gravity during the coating process. Mandrel 40 can also bemade from a polymeric material which is lubricious, strong, has gooddimensional stability, and is chemically resistant to the polymersolution utilized for dip-coating, e.g., fluoropolymers, polyacetal,polyester, polyamide, polyacrylates, etc.

Moreover, mandrel 40 can be made to have a smooth surface for thepolymeric solution to form upon. In other variations, mandrel 40 candefine a surface that is coated with a material such aspolytetrafluoroethylene to enhance removal of the polymeric substrateformed thereon. In yet other variations, mandrel 40 can be configured todefine any number of patterns over its surface, e.g., either over itsentire length or just a portion of its surface, that can bemold-transferred during the dip-coating process to the inner surface ofthe first layer of coating of the dip-coated substrate tube. Thepatterns can form raised or depressed sections to form various patternssuch as checkered, cross-hatched, cratered, etc. that can enhanceendothelialization with the surrounding tissue after the device isimplanted within a patient, e.g., within three months or ofimplantation.

The direction that mandrel 40 is dipped within polymeric solution 46 canalso be alternated or changed between layers of substrate 10. In formingsubstrates having a length ranging from, e.g., 1 cm to 40 cm or longer,substrate 10 can be removed from mandrel 40 and replaced onto mandrel 40in an opposite direction before the dipping process is continued.Alternatively, mandrel 40 can be angled relative to bracket arm 38and/or polymeric solution 46 during or prior to the dipping process.

This can also be accomplished in yet another variation by utilizing adipping assembly as illustrated in FIGS. 2B and 2C to achieve a uniformwall thickness throughout the length of the formed substrate 10 per dip.For instance, after 1 to 3 coats are formed in a first dippingdirection, additional layers formed upon the initial layers can beformed by dipping mandrel 40 in a second direction opposite to the firstdipping direction, e.g., angling the mandrel 40 anywhere up to 180° fromthe first dipping direction. This can be accomplished in one examplethrough the use of one or more pivoting linkages 56, 58 connectingmandrel 40 to bracket arm 38, as illustrated. The one or more linkages56, 58 can maintain mandrel 40 in a first vertical position relative tosolution 46 to coat the initial layers of substrate 10, as shown in FIG.2B. Linkages 56, 58 can then be actuated to reconfigure mandrel 40 fromits first vertical position to a second vertical position opposite tothe first vertical position, as indicated by direction 59 in FIG. 2C.With repositioning of mandrel 40 complete, the dipping process can beresumed by dipping the entire linkage assembly along with mandrel 40 andsubstrate 10. In this manner, neither mandrel 40 nor substrate 10 needsto be removed and thus eliminates any risk of contamination. Linkages56, 58 can comprise any number of mechanical or electromechanicalpivoting and/or rotating mechanisms as known in the art.

Dipping mandrel 40 and substrate 10 in different directions can alsoenable the coated layers to have a uniform thickness throughout from itsproximal end to its distal end to help compensate for the effects ofgravity during the coating process. These values are intended to beillustrative and are not intended to be limiting in any manner. Anyexcess dip-coated layers on the linkages 56, 58 can simply be removedfrom mandrel 40 by breaking the layers. Alternating the dippingdirection can also result in the polymers being oriented alternatelywhich can reinforce the tensile strength in the axial direction of thedip coated tubular substrate 10.

With dip-coating assembly 30, one or more high molecular weightbiocompatible and/or bioabsorbable polymers can be selected for formingupon mandrel 40. Examples of polymers which can be utilized to form thepolymeric substrate can include, but is not limited to, polyethylene,polycarbonates, polyamides, polyesteramides, polyetheretherketone,polyacetals, poly ketals, polyurethane, polyolefin, or polyethyleneterephthalate and degradable polymers, for example, polylactide (PLA)including poly-L-lactide (PLLA), poly-glycolide (PGA),poly(lactide-co-glycolide) (PLGA) or polycaprolactone, caprolactones,polydioxanones, poly anhydrides, poly orthocarbonates, polyphosphazenes,chitin, chitosan, poly(amino acids), and polyorthoesters, andcopolymers, terpolymers and combinations and mixtures thereof.

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polylactic acid, polyglycolic acid,polydimethylsiloxanes, and polyetherketones.

Examples of biodegradable polymers which can be used for dip-coatingprocess are polylactide (PLA), polyglycolide (PGA),poly(lactide-co-glycolide) (PLGA), poly-ϵ-caprolactone (PCL),polydioxanone, polyanhydride, trimethylene carbonate,poly(β-hydroxybutyrate), poly(g-ethyl glutamate), poly(DTHiminocarbonate), poly(bisphenol A iminocarbonate), poly(ortho ester),polycyanoacrylate, and polyphosphazene, and copolymers, terpolymers andcombinations and mixtures thereof. There are also a number ofbiodegradable polymers derived from natural sources such as modifiedpolysaccharides (e.g., cellulose, chitin, chitosan, or dextran) ormodified proteins (e.g., fibrin or casein).

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polylactic acid, polyglycolic acid,polydimethylsiloxanes, and polyetherketones.

These examples of polymers which can be utilized for forming thesubstrate are not intended to be limiting or exhaustive but are intendedto be illustrative of potential polymers which can be used. As thesubstrate can be formed to have one or more layers overlaid upon oneanother, the substrate can be formed to have a first layer of a firstpolymer, a second layer of a second polymer, and so on depending uponthe desired structure and properties of the substrate. Thus, the varioussolutions and containers can be replaced beneath mandrel 40 betweendip-coating operations in accordance with the desired layers to beformed on the substrate such that the mandrel 40 can be dippedsequentially into the appropriate polymeric solution.

Depending upon the desired wall thickness of the formed substrate, themandrel 40 can be dipped into the appropriate solution as determined bythe number of times the mandrel 40 is immersed, the duration of time ofeach immersion within the solution, as well as the delay time betweeneach immersion or the drying or curing time between dips. Additionally,parameters such as the dipping and/or withdrawal rate of the mandrel 40from the polymeric solution can also be controlled to range from, e.g.,5 mm/min to 1000 mm/min. Formation via the dip-coating process canresult in a polymeric substrate having half the wall thickness whileretaining an increased level of strength in the substrate as compared toan extruded polymeric structure. For example, to form a substrate havinga wall thickness of, e.g., 200 μm, built up of multiple layers ofpolylactic acid, mandrel 40 can be dipped between, e.g., 2 to 20 timesor more, into the polymeric solution with an immersion time rangingfrom, e.g., 15 seconds (or less) to 240 minutes (or more). Moreover, thesubstrate and mandrel 40 can be optionally dried or cured for a periodof time ranging from, e.g., 15 seconds (or less) to 60 minutes (or more)between each immersion. These values are intended to be illustrative andare not intended to be limiting in any manner.

Aside from utilizing materials which are relatively high in molecularweight, another parameter which can be considered in further increasingthe ductility of the material is its crystallinity, which refers to thedegree of structural order in the polymer. Such polymers can contain amixture of crystalline and amorphous regions such that reducing thepercentage of the crystalline regions in the polymer can furtherincrease the ductility of the material. Polymeric materials not onlyhaving a relatively high molecular weight but also having a relativelylow crystalline percentage can be utilized in the processes describedherein to form a desirable tubular substrate.

The following Table 1 show examples of various polymeric materials(e.g., PLLA IV 8.28 and PDLLA 96/4) to illustrate the molecular weightsof the materials in comparison to their respective crystallinitypercentage. The glass transition temperature, T_(g), as well as meltingtemperature, T_(m), are given as well. An example of PLLA IV 8.28 isshown illustrating the raw resin and tube form as having the samemolecular weight, M_(w), of 1.70×10⁶ gram/mol. However, thecrystallinity percentage of PLLA IV 8.28 Resin is 61.90% while thecorresponding Tube form is 38.40%. Similarly for PDLLA 96/4, the resinform and tube form each have a molecular weight, M_(w), of 9.80×10⁵gram/mol; however, the crystallinity percentages are 46.20% and 20.90%,respectively.

TABLE 1 Various polymeric materials and their respective crystallinitypercentages. Crystallinity M_(w) Material T_(g) (° C.) T_(m) (° C.) (%)(gram/mol) PLLA IV8.28 72.5 186.4 61.90% 1.70 × 10⁶ Resin PLLA IV8.2873.3 176.3 38.40% 1.70 × 10⁶ Tubes PDLLA 96/4 61.8 155.9 46.20% 9.80 ×10⁵ Resin PDLLA 96/4 60.3 146.9 20.90% 9.80 × 10⁵ Tubes

As the resin is dip coated to form the tubular substrate through themethods described herein, the drying procedures and processing help topreserve the relatively high molecular weight of the polymer from thestarting material and throughout processing to substrate and stentformation. Moreover, the drying process in particular can facilitate theformation of desirable crystallinity percentages, as described above.

Aside from the crystallinity of the materials, the immersion times aswell as drying times can be uniform between each immersion or they canbe varied as determined by the desired properties of the resultingsubstrate. Moreover, the substrate can be placed in an oven or dried atambient temperature between each immersion or after the final immersionto attain a predetermined level of crystals, e.g., 60%, and a level ofamorphous polymeric structure, e.g., 40%. Each of the layers overlaidupon one another during the dip-coating process can be tightly adheredto one another and the mechanical properties of each polymer areretained in their respective layer with no limitation on the molecularweight of the polymers utilized.

Varying the drying conditions of the materials can also be controlled toeffect desirable material parameters. The polymers can be dried at orabove the glass transition temperature (e.g., 10° to 20° C. above theglass transition temperature, T_(g)) of the respective polymer toeffectively remove any residual solvents from the polymers to attainresidual levels of less than 100 ppm, e.g., between 20 to 100 ppm.Positioning of the polymer substrate when drying is another factor whichcan be controlled as affecting parameters, such as geometry, of thetube. For instance, the polymer substrate can be maintained in a dryingposition such that the substrate tube is held in a perpendicularposition relative to the ground such that the concentricity of the tubesis maintained. The substrate tube can be dried in an oven at or abovethe glass transition temperature, as mentioned, for a period of timeranging anywhere from, e.g., 10 days to 30 days or more. However,prolonged drying for a period of time, e.g., greater than 40 days, canresult in thermal degradation of the polymer material.

Additionally and/or optionally, a shape memory effect can be induced inthe polymer during drying of the substrate. For instance, a shape memoryeffect can be induced in the polymeric tubing to set the tubular shapeat the diameter that was formed during the dip-coating process. Anexample of this is to form a polymeric tube by a dip-coating processdescribed herein at an outer diameter of 5 mm and subjecting thesubstrate to temperatures above its glass transition temperature, T_(g).At its elevated temperature, the substrate can be elongated, e.g., froma length of 5 cm to 7 cm, while the outer diameter of the substrate isreduced from about 5.0 mm to about 3.0 mm. Of course, these examples aremerely illustrative and the initial diameter can generally rangeanywhere from, e.g., 3 mm to 9 mm, and the reduced diameter cangenerally range anywhere from, e.g., 1.5 mm to 5 mm, provided thereduced diameter is less than the initial diameter.

Once lengthened and reduced in diameter, the substrate can be quenchedor cooled in temperature to a sub-T_(g) level, e.g., about 20° C. belowits T_(g), to allow for the polymeric substrate to transition back toits glass state. This effectively imparts a shape memory effect ofself-expansion to the original diameter of the substrate. When such atube (or stent formed from the tubular substrate) is compressed orexpanded to a smaller or larger diameter and later exposed to anelevated temperature, over time the tube (or stent) can revert to itsoriginal 5 mm diameter. This post-processing can also be useful forenabling self-expansion of the substrate after a process like lasercutting (e.g., when forming stents or other devices for implantationwithin the patient) where the substrate tube is typically heated to itsglass transition temperature, T_(g).

An example of a substrate having multiple layers is illustrated in FIGS.3A and 3B which show partial cross-sectional side views of an example ofa portion of a multi-layer polymeric substrate formed along mandrel 40and the resulting substrate. Substrate 10 can be formed along mandrel 40to have a first layer 60 formed of a first polymer, e.g.,poly(l-lactide). After the formation of first layer 60, an optionalsecond layer 62 of polymer, e.g., poly(L-lactide-co-glycolide), can beformed upon first layer 60. Yet another optional third layer 64 ofpolymer, e.g., poly(d,l-lactide-co-glycolide), can be formed upon secondlayer 62 to form a resulting substrate defining a lumen 66 therethroughwhich can be further processed to form any number of devices, such as astent. One or more of the layers can be formed to degrade at a specifiedrate or to elute any number of drugs or agents.

An example of this is illustrated in the cross-sectional end view ofFIG. 3C, which shows an exemplary substrate having three layers 60, 62,64 formed upon one another, as above. In this example, first layer 60can have a molecular weight of M_(n1), second layer 62 can have amolecular weight of M_(n2), and third layer 64 can have a molecularweight of M_(n3). A stent fabricated from the tube can be formed suchthat the relative molecular weights are such where M_(n1)>M_(n2)>M_(n3)to achieve a preferential layer-by-layer degradation through thethickness of the tube beginning with the inner first layer 60 andeventually degrading to the middle second layer 62 and finally to theouter third layer 64 when deployed within the patient body.Alternatively, the stent can be fabricated where the relative molecularweights are such where M_(n1)<M_(n2)<M_(n3) to achieve a layer-by-layerdegradation beginning with the outer third layer 64 and degradingtowards the inner first layer 60. This example is intended to beillustrative and fewer than or more than three layers can be utilized inother examples. Additionally, the molecular weights of each respectivelayer can be altered in other examples to vary the degradation ratesalong different layers, if so desired.

Moreover, any one or more of the layers can be formed to impartspecified mechanical properties to the substrate 10 such that thecomposite mechanical properties of the resulting substrate 10 canspecifically tuned or designed. Additionally, although three layers areillustrated in this example, any number of layers can be utilizeddepending upon the desired mechanical properties of the substrate 10.

Moreover, as multiple layers can be overlaid one another in forming thepolymeric substrate, specified layers can be designated for a particularfunction in the substrate. For example, in substrates which are used tomanufacture polymeric stents, one or more layers can be designed asload-bearing layers to provide structural integrity to the stent whilecertain other layers can be allocated for drug-loading or eluting. Thoselayers which are designated for structural support can be formed fromhigh-molecular weight polymers. e.g., PLLA or any other suitable polymerdescribed herein, to provide a high degree of strength by omitting anydrugs as certain pharmaceutical agents can adversely affect themechanical properties of polymers. Those layers which are designated fordrug-loading can be placed within, upon, or between the structurallayers.

Additionally, multiple layers of different drugs can be loaded withinthe various layers. The manner and rate of drug release from multiplelayers can depend in part upon the degradation rates of the substratematerials. For instance, polymers which degrade relatively quickly canrelease their drugs layer-by-layer as each successive layer degrades toexpose the next underlying layer. In other variations, drug release cantypically occur from a multilayer matrix via a combination of diffusionand degradation. In one example, a first layer can elute a first drugfor, e.g., the first 30 to 40 days after implantation. Once the firstlayer has been exhausted or degraded, a second underlying layer having asecond drug can release this drug for the next 30 to 40 days, and so onif so desired. In the example of FIG. 3B, for a stent (or otherimplantable device) manufactured from substrate 10, layer 64 can containthe first drug for release while layer 62 can contain the second drugfor release after exhaustion or degradation of layer 64. The underlyinglayer 60 can omit any pharmaceutical agents to provide uncompromisedstructural support to the entire structure.

In other examples, rather than having each successive layer elute itsrespective drug, each layer 62, 64 (optionally layer 60 as well), canelute its respective drug simultaneously or at differing rates via acombination of diffusion and degradation. Although three layers areillustrated in this example, any number of layers can be utilized withany practicable combination of drugs for delivery. Moreover, the releasekinetics of each drug from each layer can be altered in a variety ofways by changing the formulation of the drug-containing layer.

Examples of drugs or agents which can be loaded within certain layers ofsubstrate 10 can include one or more anti-proliferative,anti-neoplastic, anti-genic, anti-inflammatory, and/or anti-restenoticagents. The therapeutic agents can also include anti-lipid,antimitotics, metalloproteinase inhibitors, anti-sclerosing agents.Therapeutic agents can also include peptides, enzymes, radio isotopes oragents for a variety of treatment options. This list of drugs or agentsis presented to be illustrative and is not intended to be limiting.

Similarly, certain other layers can be loaded with radio-opaquesubstances such as platinum, gold, etc. to enable visibility of thestent under imaging modalities such as fluoroscopic imaging.Radio-opaque substances like tungsten, platinum, gold, etc. can be mixedwith the polymeric solution and dip-coated upon the substrate such thatthe radio-opaque substances form a thin sub-micron thick layer upon thesubstrate. The radio-opaque substances can thus become embedded withinlayers that degrade in the final stages of degradation or within thestructural layers to facilitate stent visibility under an imagingmodality, such as fluoroscopy, throughout the life of the implanteddevice before fully degrading or losing its mechanical strength.Radio-opaque marker layers can also be dip-coated at one or both ends ofsubstrate 10, e.g., up to 0.5 mm from each respective end. Additionally,the radio-opaque substances can also be spray-coated or cast along aportion of the substrate 10 between its proximal and distal ends in aradial direction by rotating mandrel 40 when any form of radio-opaquesubstance is to be formed along any section of length of substrate 10.Rings of polymers having radio-opaque markers can also be formed as partof the structure of the substrate 10.

Polymeric stents and other implantable devices made from such substratescan accordingly retain the material properties from the dip-coatedpolymer materials. The resulting stents, for instance, can exhibitmechanical properties which have a relatively high percentage ductilityin radial, torsional, and/or axial directions. An example of this is aresulting stent having an ability to undergo a diameter reduction ofanywhere between 5% to 70% when placed under an external load withoutany resulting plastic deformation. Such a stent can also exhibit highradial strength with, e.g., a 20% radial deformation when placed under a0.1 N to 20 N load. Such a stent can also be configured to self-expandwhen exposed to normal body temperatures.

The stent can also exhibit other characteristic mechanical propertieswhich are consistent with a substrate formed as described herein, forinstance, high ductility and high strength polymeric substrates. Suchsubstrates (and processed stents) can exhibit additional characteristicssuch as a percent reduction in diameter of between 5% to 70% withoutfracture formation when placed under a compressive load as well as apercent reduction in axial length of between 10% to 30% without fractureformation when placed under an axial load. Because of the relativelyhigh ductility, the substrate or stent can also be adapted to curve upto 180° about a 1 cm curvature radius without fracture formation orfailure. Additionally, when deployed within a vessel, a stent can alsobe expanded, e.g., by an inflatable intravascular balloon, by up to 5%to 70% to regain diameter without fracture formation or failure.

These values are intended to illustrate examples of how a polymerictubing substrate and a resulting stent can be configured to yield adevice with certain mechanical properties. Moreover, depending upon thedesired results, certain tubes and stents can be tailored for specificrequirements of various anatomical locations within a patient body byaltering the polymer and/or copolymer blends to adjust variousproperties such as strength, ductility, degradation rates, etc.

Dip-coating can be used to impart an orientation between layers (e.g.,linear orientation by dipping; radial orientation by spinning themandrel, etc.) to further enhance the mechanical properties of theformed substrate. As radial strength is a desirable attribute of stentdesign, post-processing of the formed substrate can be accomplished toimpart such attributes. Typically, polymeric stents suffer from havingrelatively thick walls to compensate for the lack of radial strength,and this, in turn, reduces flexibility, impedes navigation, and reducesarterial luminal area immediately post-implantation. Post-processing canalso help to prevent material creep and recoil (creep is atime-dependent permanent deformation that occurs to a specimen understress, typically under elevated temperatures) which are problemstypically associated with polymeric stents.

In further increasing the radial or circumferential strength of thepolymeric substrate, a number of additional processes can be applied tothe substrate after the dip-coating procedure is completed (or close tobeing completed). A polymer that is amorphous or that is partiallyamorphous will generally undergo a transition from a pliable, elasticstate (at higher temperatures) to a brittle glass-like state (at lowertemperature) as it transitions through a particular temperature,referred as the glass transition temperature (T_(g)). The glasstransition temperature for a given polymer will vary, depending on thesize and flexibility of side chains, as well as the flexibility of thebackbone linkages and the size of functional groups incorporated intothe polymer backbone. Below T_(g), the polymer will maintain someflexibility and can be deformed to a new shape. However, the further thetemperature below T_(g) the polymer is when being deformed, the greaterthe force needed to shape it.

Moreover, when a polymer is in glass transition temperature itsmolecular structure can be manipulated to form an orientation in adesired direction. Induced alignment of polymeric chains or orientationimproves mechanical properties and behavior of the material. Molecularorientation is typically imparted by application of force while thepolymer is in a pliable, elastic state. After sufficient orientation isinduced, the temperature of the polymer is reduced to prevent reversaland dissipation of the orientation.

In one example, the polymeric substrate can be heated to increase itstemperature along its entire length or along a selected portion of thesubstrate to a temperature that is at or above the T_(g) of the polymer.For instance, for a substrate fabricated from PLLA, the substrate can beheated to a temperature between 60° C. to 70° C. Once the substrate hasreached a sufficient temperature such that enough of its molecules havebeen mobilized, a force can be applied from within the substrate oralong a portion of the substrate to increase its diameter from a firstdiameter D₁ to a second increased diameter D₂ for a period of timenecessary to set the increased diameter. During this setting period, theapplication of force induces a molecular orientation in acircumferential direction to align the molecular orientation of polymerchains to enhance its mechanical properties. The re-formed substrate canthen be cooled to a lower temperature typically below T_(g), forexample, by passing the tube through a cold environment, typically dryair or an inert gas to maintain the shape at diameter D₂ and preventdissipation of molecular orientation.

The force applied to the substrate can be generated by a number ofdifferent methods. One method is by utilizing an expandable pressurevessel placed within the substrate. Another method is by utilizing abraided structure, such as a braid made from a super-elastic or shapememory alloy like NiTi alloy, to increase in size and to apply thedesirable degree of force against the interior surface of the substrate.

Yet another method can apply the expansion force by application of apressurized inert gas such as nitrogen within the substrate lumen.

A polymeric substrate can also be formed, e.g., also via dip-coating,upon a mandrel to form a base polymeric substrate 70, as shown in FIG.4A. The base polymeric substrate 70 can refer to another instance of thebase polymeric substrate 10. In other variations, the base polymericsubstrate 70 can be formed of an elastomeric bioabsorbable polymer, suchas, but not limited to, poly-ϵ-caprolactone (PCL) or trimethylenecarbonate (TMC), which can be dissolved in a compatible solvent such asdichloromethane (DCM).

The polymeric solution can be poured into a container and placed underthe dip-coating assembly 30 in an inert environment. A mandrel that isattached to the dip-coating assembly 30 can be immersed into thesolution to create the base layer of the composite stent structure. Onceformed, the resulting polymeric substrate 70 can have an initialdiameter, e.g., ranging generally from 2 mm to 10 mm, defined by themandrel which is similar to the diameter of the ring structures 12. Thesubstrate 70 can be formed to have an initial length ranging from 5 mmto 500 mm. The substrate 70 can be left upon the mandrel or removed andplaced upon another mandrel.

In one variation, the ring structures 12 can be positioned upon the basepolymeric substrate 70, as illustrated in FIG. 4B, at uniform intervalsor at predetermined non-uniform distances from one another. The spacingbetween the ring structures 12 can be determined in part by the degreeof flexibility desired of the resulting composite stent structure wherethe closer adjacent ring structures 12 are positioned relative to oneanother, the lesser resulting overall stent flexibility. Additionally,ring structures 12 can be positioned relatively closer to one anotheralong a first portion of the composite stent and relatively farther fromone another along a second portion of the stent. In one example, thering structures 12 can be positioned at a uniform distance of 1 mm to 10mm from one another.

If the ring structures 12 are formed to have a diameter which isslightly larger than a diameter of the base polymeric substrate 70, thering structures 12 can be compressed to reduce their diameters such thatthe ring structures 12 are overlaid directly upon the outer surface ofthe substrate 70. In use, the ring structures 12 can be compressed to asecond smaller diameter for delivery through the vasculature of apatient to a region to be treated. When deployed, the ring structures 12(as well as the base substrate 70 and overlaid substrate 71) can beexpanded back to their initial diameter or to a diameter less than theinitial diameter.

The ring and substrate structure can then be immersed again in the sameor different polymeric solution as base polymeric substrate 70 to forman additional polymeric substrate 71 overlaid upon the base substrate 70and ring structures 12 to form the composite stent structure 72, asillustrated in FIG. 4C. The ring structures 12 can be encapsulated orotherwise encased entirely between the base substrate 70 and theoverlaid substrate 71 such that the ring structures 12 are connected orotherwise attached to one another entirely via the elastomeric sections.

Additionally, either or both of the ring structures 12 and base oroverlaid substrate layers 70, 71 can be configured to retain and deliveror elute any number of pharmaceutical agents, such as ananti-proliferative, an anti-restenotic, etc.

Because the elastomeric polymer substrate couples the ring structures 12to one another rather than an integrated structural connecting memberbetween the ring structures themselves, the ring structures 12 can beadjustable along an axial or radially direction independent of oneanother allowing for any number of configurations and adjustments of thestent structure 72 for conforming within and bending with a vessel whichother coated stent structures are unable to achieve.

This resulting stent structure 72 can be removed from the mandrel andmachined to length, if necessary, and additional post-processing can beperformed upon the stent as well. For instance, the stent structure 72can have one or more of the ring structures 12 machined into patternedpolymeric rings 75 such as expandable scaffold structures, e.g., bylaser machining, as illustrated in FIG. 5. In machining the stentstructure, the process of removing material from the polymeric rings 75can at least partially expose portions of the polymeric rings 75 to theenvironment. For example, the inner surfaces and the outer surfaces ofthe polymeric rings 75 can remain coated or covered by both respectivebase and overlaid substrate layers 70, 71 while side surfaces of therings 75 can become exposed by removal of the substrate layers as wellas portions of the ring material as the stent structure is machined.These exposed surfaces can be re-coated, if desired, or left exposed tothe environment.

The polymeric ring structures 12 utilized in the composite stentstructure 72 can be fabricated from a common substrate and commonpolymers. However, in other variations, the ring structures forming thestent 24 can be fabricated from different substrates having differentmaterial characteristics. FIG. 6 illustrates an example where a firstset of polymeric rings 76 can be positioned in an alternating patternwith a second set of polymeric rings 77 along the base substrate 70. Inthis and other examples, the overlaid polymeric substrate 71 can beomitted from the figures merely for clarity.

Another variation is illustrated in FIG. 7, which shows an example wherea first set of polymeric ring structures 12 can be positioned along thestent with a flexible polymeric ring 73 fabricated to be relatively moreflexible than the remaining ring structures 12 positioned along aterminal end of the stent structure.

Yet another example is illustrated in FIG. 8 where each of the ringstructures can be fabricated from different substrates and polymers. Forexample, a stent structure can be fabricated to have a first polymericring 92, a second polymeric ring 93, a third polymeric ring 94, a fourthpolymeric ring 95, a fifth polymeric ring 96, and so on to form acomposite stent structure. An example of use can include a compositestent structure for placement within a tapered or diametricallyexpanding vessel where each subsequent ring structure can be fabricatedto be more radially expandable than an adjacent ring structure, e.g.,where the first polymeric ring 92 can be radially expandable to a firstdiameter, second polymeric ring 93 is radially expandable to a seconddiameter larger than the first diameter, third polymeric ring 94 can beradially expandable to a third diameter larger than the second diameter,and so on. This is intended to be exemplary and other examples are, ofcourse, intended to be within the scope of this disclosure.

Yet another variation is shown in FIG. 9, which illustrateslongitudinally-oriented polymeric strips 97 rather than ring structurespositioned along the base substrate 70. In this example, such acomposite stent structure can be configured to allow for greaterflexibility under radial stresses. Another example is illustrated inFIG. 10 which shows a helically-oriented polymeric member 98 which canbe positioned along base substrate 70.

As described in U.S. patent application Ser. No. 12/143,659 incorporatedhereinabove, the polymeric substrate utilized to form the ringstructures can be heat treated at, near, or above the glass transitiontemperature T_(g) of the substrate to set an initial diameter and thesubstrate can then be processed to produce the ring structures having acorresponding initial diameter. The resulting composite stent structurecan be reduced from its initial diameter to a second delivery diameterwhich is less than the initial diameter such that the composite stentstructure can be positioned upon, e.g., an inflation balloon of adelivery catheter. The composite stent structure at its reduced diametercan be self-constrained such that the stent remains in its reduceddiameter without the need for an outer sheath, although a sheath can beoptionally utilized. Additionally, the composite stent structure can bereduced from its initial diameter to its delivery diameter withoutcracking or material failure.

With the composite stent structure positioned upon a delivery catheter,the stent can be advanced intravascularly within the lumen 88 of avessel 86 until the delivery site is reached. The inflation balloon canbe inflated to expand a diameter of composite stent structure intocontact against the vessel interior, e.g., to an intermediate diameter,which is less than the stent's initial diameter yet larger than thedelivery diameter. The composite stent structure can be expanded to thisintermediate diameter without any cracking or failure because of theinherent material characteristics, as shown in FIG. 11A. Moreover,expansion to the intermediate diameter can allow for the composite stentstructure to securely contact the vessel wall while allowing for thewithdrawal of the delivery catheter.

Once the composite stent structure has been expanded to someintermediate diameter and secured against the vessel wall 86, thecomposite stent structure can be allowed to then self-expand furtherover a period of time into further contact with the vessel wall suchthat composite stent structure conforms securely to the tissue. Thisself-expansion feature ultimately allows for the composite stentstructure to expand back to its initial diameter which had been heat-setin the ring structures or until the composite stent structure has fullyself-expanded within the confines of the vessel lumen 88. In yet anothervariation, the composite stent structure can be expanded directly to itsfinal diameter, e.g., by balloon inflation, without having to reach anintermediate diameter and subsequent self-expansion.

In the example illustrated, a first composite stent 80 is shown deployedwithin vessel lumen 88 adjacent to a second composite stent 82 withspacing 84 between the stents. Additional stent structures can bedeployed as well depending upon the length of the lesion to be stented.FIG. 11B illustrates another example where adjacent composite stents 80,82 are deployed within vessel lumen 88 with their terminal endsoverlapping one another along overlapped portion 90. As the SFA tends todevelop long, diffuse lesions with calcification, multiple stents can bedeployed with overlapping ends. However, as this overlapping can causeregions or locations of increased stress that can initiate fracturingalong the stent and lead to potential stent failure and closure of thevessel, the terminal ring structures of both overlapped composite stents80, 82 can be fabricated from an elastomeric polymer allowing for theoverlap to occur along these segments. Such overlapping would notsignificantly compromise axial flexibility and the composite stents cancontinue its compliance with the arterial movement.

Another variation which facilitates the overlapping of adjacent stentsis shown in the side view of FIG. 12. The overlaid substrate has beenomitted for clarity only and can be included as a layer positioned atopthe base substrate 70 as well as the polymeric rings, as previouslydescribed. As illustrated, the polymeric ring structures 12 can includeterminal polymeric rings 100 which are fabricated to degrade at arelatively faster rate than the remaining ring structures 12 positionedbetween these terminal rings 100. Such a composite stent structure canallow for the optimal overlapping of multiple stents along the length ofa blood vessel.

Yet another variation is shown in the side views of FIGS. 13A and 13Bwhich illustrate a mandrel 110 that is provided with a flexiblepolymeric base substrate 112 placed or formed thereon. A set ofpolymeric ring structures 114 can be positioned along the longitudinalaxis of the flexible base coat 112 in a separate manufacturingoperation.

Another variation is illustrated in the partial cross-sectional side andend views, respectively, of FIGS. 14A and 14B. In this example, acomposite structure can be provided by forming a composite stentstructure having multiple polymeric layers. For instance, a middle layer122 can be made of a high strength polymeric material such aspoly-L-lactic acid (PLLA) or poly-L-lactide that is sandwiched betweentwo or more layers 120, 124 of a flexible polymer such aspoly-t-caprolactone (PCL). Such a composite stent structure can beconfigured to allow for greater flexibility under radial stresses whileretaining relatively high strength provided by the middle layer 122comprising PLLA.

In yet other alternative variations for forming composite structures, abioabsorbable polymeric substrate 130 initially formed by thedip-coating process as previously described can be formed into a tubularsubstrate as shown in the perspective view of FIG. 15A. Substrate 130can be further processed, such as by machining, to form a machinedsubstrate 131, as shown in the perspective view of FIG. 15B, having oneor more reduced segments 132 which are reduced in diameter alternatingwith the relatively thicker segments 134 which can be reduced indiameter to a lesser degree or uncut altogether. The number of reducedsegments 132 and the spacing between can be uniform or varied dependingupon the desired resulting stent or scaffold and the reduction indiameter of these segments 132 can also be varied as well. In oneexample, for a given initial diameter of 2 to 12 mm of substrate 130,segments 132 can be reduced in diameter by, e.g., 1.85 mm to 11.85 mm.Moreover, although the example shown in FIG. 15B shows seven reducedsegments 132 between thicker segments 134, this number can be varieddepending upon the desired resulting lengths of segments 132, e.g.,ranging from 0.5 mm to 3 mm in length.

In forming the substrate to have a variable wall thickness asillustrated, laser machining (profiling) of the outer diameter can beutilized. The integrity and material properties of the substratematerial are desirably maintained during this process of selectivelyremoving material in order to achieve the desired profile. Anultra-short pulse femtosecond type laser can be used to selectivelyremove the material from the reduced segments 132 by taking advantage,e.g., of multi-photon absorption, such that the laser removes thematerial without modifying the material integrity. Thus, the mechanicalproperties and molecular structure of the bioabsorbable substrate 130can be unaffected during this machining process.

Some of the variables in utilizing such a laser for this particularapplication can include, e.g., laser power level, laser pulse frequency,energy profile of the beam, beam diameter, lens focal length, focalposition relative to the substrate surface, speed of the substrate/beamrelative to the substrate, and any gas jet/shield either coaxial ortangential to the material, etc. By adjusting some or all of thesevariables, a multi-level profile can be readily produced. In oneexample, increasing or decreasing the rotational speed of the substraterelative to the laser during processing will vary the depth ofpenetration. This in combination with a translation rate of thesubstrate relative to the laser can also be varied to produce arelatively sharp edge in the relief area or a smooth tapered transitionbetween each of the adjacent segments. Varying both parameters along thelongitudinal axis of the substrate 130 can produce a continuouslyvariable profile from which a stent pattern can be cut, as furtherdescribed below.

The laser system can comprise an ultra-short pulse width laser operatingin the femtosecond pulse region, e.g., 100 to 500 fs typical pulsewidth, and a wavelength, λ, e.g., in the near to mid-IR range (750 to1600 nm typical λ). The pulse frequency of these lasers can range fromsingle pulse to kilohertz (1 to 10 kHz typical). The beam energy profilecan be TEM₀₀ to a high order mode (TEM₀₀ is typical, but not necessary).The beam delivery system can comprise a beam bender, vertical mountedmonocular viewing/laser beam focusing head, focusing lens and coaxialgas jet assembly. A laser system can also include a linear stage havinga horizontally mounted rotary stage with a collet clamping systemmounted below the focusing/cutting head.

With the substrate tube 130 clamped by the rotary stage and held in ahorizontal plane, the laser beam focusing head can be positionedperpendicular to the longitudinal axis of substrate 130. Moving thefocus of the beam away from the outer diameter of the tubing, anon-penetrating channel can be machined in the substrate 130.Controlling the speed of rotation and/or linear translation of the tubeunder the beam, a channel can be machined along the substrate axis.Varying any one or all of the parameters (e.g., position, depth, taper,length, etc.) of machining can be controlled and positioned along theentire length of the substrate 130. The ability to profile the substrate130 can provide a number of advantages in the flexibility of theresulting stent design and performance. For example, such profiling canimprove the flexibility of the stent geometry and expansion capabilityin high stress areas, expose single or multiple layers to enhance orexpose drug delivery by placing non-penetrating holes into one or moreparticular drug-infused layer(s) of the substrate 130 or by placinggrooves or channels into these drug layer(s). Moreover, the ability toprofile the substrate 130 can allow for a substrate having a variableprofile which can be over-coated with the same or different polymer, asdescribed herein.

Once machined substrate 131 has been sufficiently processed, it can thenbe coated, e.g., via the dip-coating process as previously described,such that one or more additional elastomeric polymer layers are coatedupon substrate 131. The example shown in the perspective view of FIG.15C illustrates machined substrate 131 having at least one additionalelastomeric polymer layer 136 coated thereupon; however, othervariations can have more than one layer coated atop one anotherdepending upon the desired characteristics of the resulting substrate.Additionally, each subsequent layer coated upon machined substrate 131can be of the same, similar, or different material from polymericsubstrate 131, e.g., polyethylene, polycarbonates, polyamides,polyesteramides, polyetheretherketone, polyacetals, poly ketals,polyurethane, polyolefin, polyethylene terephthalate, polylactide,poly-L-lactide, poly-glycolide, poly(lactide-co-glycolide),polycaprolactone, caprolactones, polydioxanones, polyanhydrides,polyorthocarbonates, polyphosphazene, chitin, chitosan, poly(aminoacids), polyorthoesters, oligomers, homopolymers, methyl acrylate,methyl methacrylate, acrylic acid, methacrylic acid, acrylamide,hydroxyethyl acrylate, hydroxyethyl methacrylate, glyceryl acrylate,glyceryl methacrylate, methacrylamide, ethacrylamide, styrene, vinylchloride, vinyl pyrrolidone, polyvinyl alcohol, polycaprolactam,polylauryl lactam, polyhexamethylene adipamide, polyhexamethylenedodecanediamide, trimethylene carbonate, poly(β-hydroxybutyrate),poly(g-ethyl glutamate), poly(DTH iminocarbonate), poly(bisphenol Aiminocarbonate), polycyanoacrylate, polyphosphazene, methyl acrylate,methyl methacrylate, acrylic acid, methacrylic acid, acrylamide,hydroxyethyl acrylate, hydroxyethyl methacrylate, glyceryl acrylate,glyceryl methacrylate, methacrylamide, ethacrylamide, and copolymers,terpolymers and combinations and mixtures thereof, etc., again dependingupon the desired resulting characteristics. The one or more polymericlayers 136 can be coated upon machined substrate 131 such that theelastomeric polymer 136 forms within the reduced segments 132 as well asupon segments 134. The resulting coated layer 136 can range in thicknessaccordingly from, e.g., 50 μm to 500 μm, such that the layer 136 forms auniform outer diameter along the length of substrate 131. As shown inthe perspective partial cutaway view of FIG. 15D, the thickenedelastomeric polymer segments 138 formed along reduced segments 132 canbe seen along substrate 131 with substrate lumen 140 definedtherethrough.

With machined substrate 131 coated with the one or more polymeric layers136, the entire formed substrate can then be processed, e.g., machined,laser-machined, etc., to form a stent or scaffold (for example, thestent or scaffold 150 shown in FIG. 16, 17, 19, or 20).

FIG. 16 is a side view of a portion of an example composite stent orscaffold 150 which can be formed (e.g., machined, laser cut, etc.) froma base polymeric substrate such as, for example, base polymericsubstrate 10 or base polymeric substrate 70.

Examples of polymers which can be utilized to form the base polymericsubstrate or layer can include, but is not limited to, polyethylene,polycarbonates, polyamides, polyesteramides, polyetheretherketone,polyacetals, polyketals, polyurethane, polyolefin, or polyethyleneterephthalate and biodegradable or bioabsorbable polymers, for example,polylactide (PLA) including poly-L-lactide (PLLA), poly-glycolide (PGA),poly(lactide-co-glycolide) (PLGA) or polycaprolactone orpoly-caprolactone (PCL), caprolactones, polydioxanones, polyanhydrides,polyorthocarbonates, polyphosphazenes, chitin, chitosan, poly(aminoacids), and polyorthoesters, and copolymers, terpolymers andcombinations, blends, or mixtures thereof.

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polylactic acid, polyglycolic acid,polydimethylsiloxanes, and polyetherketones.

Examples of other biodegradable polymers which can be used to form partof the composite stent or scaffold include, but is not limited to,trimethylene carbonate, poly(β-hydroxybutyrate), poly(g-ethylglutamate), poly(DTH iminocarbonate), poly(bisphenol A iminocarbonate),poly(ortho ester), polycyanoacrylate, and copolymers, terpolymers andcombinations and mixtures thereof. There are also a number ofbiodegradable polymers derived from natural sources such as modifiedpolysaccharides (cellulose, chitin, chitosan, dextran) or modifiedproteins (fibrin, casein).

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polyacetals, polyketals,polydimethylsiloxanes, and polyetherketones.

The example composite stent or scaffold 150 can comprise polymeric ringstructures 154 and one or more interconnecting struts 152 which extendbetween and couple adjacent ring structures 154. When the polymeric ringstructures 154 are made from a base polymeric layer which has beenformed via a dip-coating process (such as any of the dip-coatingprocesses described with respect to FIG. 2A, 2B, 2C, 3A, 3B, or 3C) orother finishing processes, the polymeric ring structures 154 can retaina molecular weight and mechanical strength of the starting substrate orthe base polymeric substrate. When the base polymeric substrate is madefrom a bioabsorbable or biodegradable polymeric substance, such as anyof PLA, PLLA, PGA, PLGA, PCL, caprolactones, polydioxanones,polyanhydrides, polyorthocarbonates, polyphosphazenes, chitin, chitosan,poly(amino acids), and polyorthoesters, copolymers thereof terpolymersthereof, or combinations and mixtures thereof, the polymeric ringstructures 154 can be bioabsorbable or biodegradable.

The polymeric ring structures 154 can be formed at a first diameter andbe radially compressible to a smaller second diameter or a deploymentdiameter. The polymeric ring structures 154 can be re-expandable orself-expandable to the larger first diameter when deployed within thevasculature of a patient. As illustrated in FIG. 16, the polymeric ringstructures 154 can be axially or longitudinally separated from oneanother and adjacent polymeric ring structures 154 can be connected orcoupled by one or more interconnecting struts 152. Each of theinterconnecting struts 152 can have a width which is less than acircumference of one of the polymeric ring structures 154. The polymericring structures 154 can be axially and rotationally movable relative toone another via the interconnecting struts 152. The one or moreinterconnecting struts 152 can also be made of bioabsorbable polymers,polymer blends, or co-polymer such that the entire composite stentstructure 150 can be bioabsorbable.

The interconnecting struts 152 can be formed from a polymer blend, ablend of polymer solutions, or co-polymer comprising poly-L-lactide(PLLA) and an elastomeric polymer. In certain variations, the polymerblend or co-polymer can have a glass transition temperature between 50°C. and 65° C.

In one variation, the elastomeric polymer can be or comprisepolycaprolactone (PCL). The PCL can be about 1% to about 10% (forexample, weight/weight or volume/volume) of the polymer blend orco-polymer. In other variations, the PCL can be about 1% to about 50%(for example, weight/weight or volume/volume) of the polymer blend orco-polymer. When the interconnecting struts 152 are made of one or moreelastomeric polymers, at least one of the interconnecting struts 152 canbe more elastic than the polymeric ring structures 154.

In one variation, the polymeric ring structures 154 can be spaced closerto one another along a first portion than along a second portion of thecomposite stent structure 150. In this and other variations, a terminalring structure (for example, a terminal ring structure positionedsimilar to the terminal ring 73 of FIG. 7) can be relatively moreflexible than a remainder of the polymeric ring structures 154.

As shown in the example composite stent or scaffold 150 of FIG. 16, theplurality of interconnecting struts 152 can be positioned along a lengthof the composite stent or scaffold 150 in a circumferentiallyalternating manner between immediately adjacent ring structures 154. Inother variations not shown in the figures, the interconnecting struts152 can be longitudinally aligned with one another along a length of thecomposite stent or scaffold 150.

In another variation, the composite stent or scaffold 150 can be formedfrom a coated substrate 131 such that the interconnecting struts 152 areformed from thickened elastomeric polymer segments 138 while thepolymeric ring structures 154 are formed on the polymeric substrate 131.This can result in a contiguous and uniform composite stent or scaffold150 which comprises high-strength circumferential segments or ringstructures 154 connected to one another via elastomeric interconnectingstruts 152 such that the composite stent or scaffold 150 exhibitshigh-strength characteristics yet is flexible overall.

FIG. 17 is a side view of a portion of a variation of a composite stentor scaffold 160 comprising a first polymeric ring structure 162 and asecond polymeric ring structure 164 connected by one or moreinterconnecting struts 152. In this variation, the first polymeric ringstructure 162 can be made from a base polymeric substrate comprising anelastomeric bioabsorbable polymer resin such as PCL or TMC while theadjacent second polymeric ring structure 164 can be made from only thebase polymeric substrate or another polymeric substrate comprising adifferent polymer blend or composition.

In yet another variation, the composite stent or scaffold 160 structurecan be formed from the coated polymeric substrate 131 such that thefirst polymeric ring structure 162 is formed from the elastomericpolymer segments 138 while an adjacent second polymeric ring structure164 is formed from polymeric substrate 131 such that the secondpolymeric ring structure 164 is relatively higher in strength than thefirst polymeric ring structure 162, which is relatively more flexible.The alternating segments of elastomeric segments and substrate segmentscan be repeated along a portion or the entire length of the compositestent or scaffold 160 depending upon the desired degree of flexibilityand strength characteristics. Moreover, other variations of alternatingbetween the segments can be employed.

FIG. 18A illustrates an example of polymeric substrate 170 which hasbeen machined to form ring segments 172 connected via one or moreinterconnecting struts 174. The polymeric substrate 170 can be initiallyformed from a dip-coated base polymeric substrate such as base polymericsubstrate 10 or base polymeric substrate 70. The dip-coated basepolymeric substrate can be machined or laser cut into a number of ringsegments 172 connected via interconnecting struts 174. Although sevenring segments 172 are shown in this example, fewer than or greater thanseven ring segments 172 can be utilized. In one variation, theinterconnecting struts 174 can be fashioned into alternating apposedmembers between adjacent ring segments 172. For example, theinterconnecting struts 174 can be positioned along a length of thepolymeric substrate 170 in a circumferentially alternating mannerbetween immediately adjacent ring segments 172. Once the polymericsubstrate 170 has been desirably machined or cut, the polymericsubstrate 170 can be positioned upon mandrel 176, as shown in FIG. 18B.

In one variation, the mandrel 176 and the entire machined polymericsubstrate 170 can then be coated again, e.g., via dip-coating aspreviously described, by one or more layers of bioabsorbable elastomericpolymers 180 (e.g., PCL). The one or more layers of bioabsorbableelastomeric polymers 180 can form thickened elastomeric interconnectingstrut sections 182 as well as thickened elastomeric ring segments 172,as shown in FIGS. 18C and 18D. In other variations not shown in FIG. 18Cbut contemplated by this disclosure, the one or more layers ofbioabsorbable elastomeric polymers 180 (e.g., PCL) can cover only theinterconnecting struts 174. All such composite machined or cutsubstrates can then be further processed, machined or cut to form one ormore composite stent or scaffolds having various unique or advantageouscomposite structural characteristics.

FIG. 19 is a side view of a portion of an example composite stent orscaffold 190. The composite stent or scaffold 190 can comprise polymericring structures 194 and one or more interconnecting struts 192 whichextend between and coupled adjacent polymeric ring structures 194.

In certain variations, the polymeric ring structures 194 can be madefrom a dip-coated base polymeric substrate such as base polymericsubstrate 10 or base polymeric substrate 70.

Examples of polymers which can be utilized to form the base polymericsubstrate or layer can include, but is not limited to, polyethylene,polycarbonates, polyamides, polyesteramides, polyetheretherketone,polyacetals, polyketals, polyurethane, polyolefin, or polyethyleneterephthalate and biodegradable or bioabsorbable polymers, for example,polylactide (PLA) including poly-L-lactide (PLLA), poly-glycolide (PGA),poly(lactide-co-glycolide) (PLGA) or polycaprolactone orpoly-ϵ-caprolactone (PCL), caprolactones, polydioxanones,polyanhydrides, polyorthocarbonates, polyphosphazenes, chitin, chitosan,poly(amino acids), and polyorthoesters, and copolymers, terpolymers andcombinations, blends, or mixtures thereof.

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polylactic acid, polyglycolic acid,polydimethylsiloxanes, and polyetherketones.

Examples of other biodegradable polymers which can be used to form partof the composite stent or scaffold include, but is not limited to,trimethylene carbonate, poly(β-hydroxybutyrate), poly(g-ethylglutamate), poly(DTH iminocarbonate), poly(bisphenol A iminocarbonate),poly(ortho ester), polycyanoacrylate, and copolymers, terpolymers andcombinations and mixtures thereof. There are also a number ofbiodegradable polymers derived from natural sources such as modifiedpolysaccharides (cellulose, chitin, chitosan, dextran) or modifiedproteins (fibrin, casein).

Other examples of suitable polymers can include synthetic polymers, forexample, oligomers, homopolymers, and co-polymers, acrylics such asthose polymerized from methyl acrylate, methyl methacrylate, acrylicacid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethylmethacrylate, glyceryl acrylate, glyceryl methacrylate, methacrylamideand ethacrylamide; vinyls such as styrene, vinyl chloride, vinylpyrrolidone, polyvinyl alcohol, and vinyls acetate; polymers formed ofethylene, propylene, and tetrafluoroethylene. Further examples caninclude nylons such as polycaprolactam, polylauryl lactam,polyhexamethylene adipamide, and polyhexamethylene dodecanediamide, andalso polyurethanes, polycarbonates, polyamides, polysulfones,poly(ethylene terephthalate), polyacetals, polyketals,polydimethylsiloxanes, and polyetherketones.

When the polymeric ring structures 194 are made from a base polymericlayer which has been formed via a dip-coating process (such as any ofthe dip-coating processes described with respect to FIG. 2A, 2B, 2C, 3A,3B, or 3C) or other finishing processes, the polymeric ring structures194 can retain a molecular weight and mechanical strength of thestarting substrate or the base polymeric substrate. In addition, whenthe base polymeric substrate is made from a bioabsorbable orbiodegradable polymeric substance, such as any of PLA, PLLA, PGA, PLGA,PCL, caprolactones, polydioxanones, polyanhydrides, polyorthocarbonates,polyphosphazenes, chitin, chitosan, poly(amino acids), andpolyorthoesters, copolymers thereof, terpolymers thereof, orcombinations and mixtures thereof, the polymeric ring structures 194 canbe bioabsorbable or biodegradable.

The polymeric ring structures 194 can be formed at a first diameter andbe radially compressible to a smaller second diameter or a deploymentdiameter. The polymeric ring structures 194 can be re-expandable orself-expandable to the larger first diameter when deployed within thevasculature of a patient. As illustrated in FIG. 19, the polymeric ringstructures 194 can be axially or longitudinally separated from oneanother and adjacent polymeric ring structures 194 can be connected orcoupled by the one or more interconnecting struts 192. Each of theinterconnecting struts 192 can have a width which is less than acircumference of one of the polymeric ring structures 194. The polymericring structures 194 can be axially and rotationally movable relative toone another via the interconnecting struts 192. The one or moreinterconnecting struts 192 can also be made of bioabsorbable polymers,polymer blends, or co-polymer such that the entire composite stentstructure 190 is bioabsorbable.

The interconnecting struts 192 can be formed from a polymer blend, ablend of polymer solutions, or co-polymer comprising poly-L-lactide(PLLA) and an elastomeric polymer. In certain variations, the polymerblend or co-polymer can have a glass transition temperature between 50°C. and 65° C.

In one variation, the elastomeric polymer can be or comprisepolycaprolactone (PCL). The PCL can be about 1% to about 10% (forexample, weight/weight or volume/volume) of the polymer blend orco-polymer. In other variations, the PCL can be about 1% to about 50%(for example, weight/weight or volume/volume) of the polymer blend orco-polymer. When the interconnecting struts 192 are made of one or moreelastomeric polymers, at least one of the interconnecting struts 192 canbe more elastic than the polymeric ring structures 194.

In one variation, the polymeric ring structures 194 can be spaced closerto one another along a first portion than along a second portion of thecomposite stent structure 190. In this and other variations, a terminalring structure (for example, a terminal ring structure positionedsimilar to the terminal ring 73 of FIG. 7) can be relatively moreflexible than a remainder of the polymeric ring structures 194.

As shown in the example composite stent or scaffold 190 of FIG. 19, theplurality of interconnecting struts 192 can be positioned along a lengthof the composite stent or scaffold 190 in a circumferentiallyalternating manner between immediately adjacent ring structures 194. Inother variations not shown in the figures, the interconnecting struts192 can be longitudinally aligned with one another along a length of thecomposite stent or scaffold 190.

In another variation, the interconnecting struts 192 can be formed fromthe thickened elastomeric interconnecting strut sections 182 while thepolymeric ring structures 194 can be formed from the ring segments 172.

The resulting composite stent or scaffold 190 allows for the structureto have significant flexibility along the axial, torsional, and/orbending directions as well as the ability to withstand relatively longfatigue cycles without formation of cracks or fractures, e.g., 1,000,000to 3,000,000 cycles, in axial compression, extension, and torsionalmodes. Also, the stent or scaffold 190 can also withstand a pulsatilefatigue life of up to, e.g., 120,000,000 cycles or more.

FIG. 20 is a side view of a portion of a variation of a composite stentor scaffold 200 comprising a first polymeric ring structure 202 and asecond polymeric ring structure 204 connected by one or moreinterconnecting struts 192. In this variation, the first polymeric ringstructure 202 can be made from a base polymeric substrate comprising anelastomeric bioabsorbable polymer resin such as PCL, TMC, or DCM whilethe adjacent second polymeric ring structure 204 can be made from onlythe base polymeric substrate or another polymeric substrate comprising adifferent polymer blend or composition. In this and other variations,the interconnecting struts 192 can also alternate such that oneinterconnecting strut 192 can be elastomeric while another adjacent orneighboring interconnecting strut 192 can be non-elastomeric or be madefrom a polymeric blend or solution having a different percentage ofelastomeric polymers.

The applications of the disclosed invention discussed above are notlimited to certain processes, treatments, or placement in certainregions of the body, but can include any number of other processes,treatments, and areas of the body. Modification of the above-describedmethods and devices for carrying out the invention and variations ofaspects of the invention that are obvious to those of skill in the artsare intended to be within the scope of this disclosure. Moreover,various combinations of aspects between examples are also contemplatedand are considered to be within the scope of this disclosure as well.

What is claimed is:
 1. A bioabsorbable composite stent structure,comprising: bioabsorbable polymeric ring structures which retain amolecular weight and mechanical strength of a starting substrate, thering structures having a formed first diameter and being radiallycompressible to a smaller second diameter and re-expandable to the firstdiameter, wherein the ring structures are separated from one another andcomprise a base polymeric layer; one or more interconnecting strutswhich extend between and couple adjacent ring structures, wherein theinterconnecting struts each has a width which is less than acircumference of one of the ring structures, wherein the interconnectingstruts are formed from a polymer blend or co-polymer of poly-L-lactide(PLLA) and an elastomeric polymer, wherein the adjacent ring structuresare axially and rotationally movable relative to one another via theinterconnecting struts, and wherein the one or more interconnectingstruts are bioabsorbable.
 2. The stent structure of claim 1, wherein theelastomeric polymer is polycaprolactone (PCL).
 3. The stent structure ofclaim 2, wherein the PCL is 1% to 10% of the polymer blend orco-polymer.
 4. The stent structure of claim 2, wherein the PCL is 1% to50% of the polymer blend or co-polymer.
 5. The stent structure of claim1, wherein the polymer blend or co-polymer has a glass transitiontemperature between 50° C. and 65° C.
 6. The stent structure of claim 1,wherein the ring structures are spaced closer to one another along afirst portion than along a second portion of the stent structure.
 7. Thestent structure of claim 1, wherein a terminal ring structure isrelatively more flexible than a remainder of the ring structures.
 8. Thestent structure of claim 1, wherein the base polymeric layer is abioabsorbable polymeric substrate formed via a dip-coating process.
 9. Abioabsorbable composite stent structure, comprising: bioabsorbablepolymeric ring structures which retain a molecular weight and mechanicalstrength of a starting substrate, the ring structures having a formedfirst diameter and being radially compressible to a smaller seconddiameter and re-expandable to the first diameter, wherein the ringstructures are separated from one another and comprise a base polymericlayer; a plurality of interconnecting struts which extend between andcouple adjacent ring structures, wherein the interconnecting struts eachhas a width which is less than a circumference of one of the ringstructures, wherein the interconnecting struts are formed from a polymerblend or co-polymer of poly-L-lactide (PLLA) and an elastomeric polymer,wherein the plurality of interconnecting struts are positioned along alength of the stent structure in a circumferentially alternating mannerbetween immediately adjacent ring structures, wherein the ringstructures are spaced closer to one another along a first portion thanalong a second portion of the stent structure, and wherein the one ormore interconnecting struts are bioabsorbable.
 10. The stent structureof claim 9, wherein the elastomeric polymer is polycaprolactone (PCL).11. The stent structure of claim 10, wherein the PCL is 1% to 10% of thepolymer blend or co-polymer.
 12. The stent structure of claim 10,wherein the PCL is 1% to 50% of the polymer blend or co-polymer.
 13. Thestent structure of claim 9, wherein the polymer blend or co-polymer hasa glass transition temperature between 50° C. and 65° C.
 14. The stentstructure of claim 9, wherein the base polymeric layer is abioabsorbable polymeric substrate formed via a dip-coating process. 15.A bioabsorbable composite stent structure, comprising: bioabsorbablepolymeric ring structures which retain a molecular weight and mechanicalstrength of a starting substrate, the ring structures having a formedfirst diameter and being radially compressible to a smaller seconddiameter and re-expandable to the first diameter, wherein the ringstructures are separated from one another and comprise a base polymericlayer; one or more interconnecting struts which extend between andcouple adjacent ring structures, wherein the interconnecting struts eachhas a width which is less than a circumference of one of the ringstructures, wherein the interconnecting struts are formed from a polymerblend or co-polymer of poly-L-lactide (PLLA) and an elastomeric polymer,wherein the one or more interconnecting struts is more elastic than thering structures, wherein a terminal ring structure is relatively moreflexible than a remainder of the ring structures, and wherein the one ormore interconnecting struts are bioabsorbable.
 16. The stent structureof claim 15, wherein the elastomeric polymer is polycaprolactone (PCL).17. The stent structure of claim 16, wherein the PCL is 1% to 10% of thepolymer blend or co-polymer.
 18. The stent structure of claim 16,wherein the PCL is 1% to 50% of the polymer blend or co-polymer.
 19. Thestent structure of claim 15, wherein the polymer blend or co-polymer hasa glass transition temperature between 50° C. and 65° C.
 20. The stentstructure of claim 15, wherein the base polymeric layer is abioabsorbable polymeric substrate formed via a dip-coating process.